HLA in AA: innocent bystander or culprit?

In this issue of Blood, 2 papers deal with HLA in patients with acquired idiopathic aplastic anemia (AA). Pagliuca et al(1) show that patients with AA have a reduced structural divergence of homologous HLA alleles, possibly contributing to reduced T-cell receptor repertoire diversity, cross-reactivity, and emergence of autoreactive T-cell clones. In parallel, Zaimoku et al(2) document that somatic mutations in HLA genes leading to functional loss are frequent and correlate with clinical manifestations of AA, such as age onset and risk of clonal evolution.